A number of implantable bioprosthetic devices are currently being used for treating patients with cardiovascular diseases and defects. Such implantable devices are useful for replacing diseased, damaged, or congenitally malformed components of the patient""s cardiovascular system. Thus, damaged or diseased heart valves have been replaced with chemically-fixed, bioprosthetic heart valves prepared from tissues of porcine or bovine origin. Similarly, regions of damaged or diseased blood vessels may also be replaced with bioprosthetic vessels prepared from bovine tissues. In addition, patches made from bovine pericardium may be used for various types of tissue repair.
Typically, the animal tissues used to form implantable devices or to repair damaged tissues are chemically cross-linked with agents such as glutaraldehyde, especially those animal tissue components that come into direct contact with the patient""s blood. Such treatment is necessary to prevent rejection of the implanted bioprosthetic device by the recipient. Such treatment also stabilizes the protein components of the animal tissue components of the device making them more resistant to degradation by proteolytic enzymes.
To prevent transmission of disease causing micro-organisms to the patient, it is necessary that the implantable tissue components and the bioprosthetic devices made therefrom be sterilized and stored in a sterile condition prior to use. Currently, bioprosthetic devices are sterilized by immersion in formaldehyde. The sterilized devices are then stored in a dilute aqueous solution containing formaldehyde and/or glutaraldehyde to maintain the tissue components in a hydrated state and to kill microbes. Because formaldehyde and glutaraldehyde are both irritants and suspected carcinogens, the bioprosthetic devices that are stored in solutions containing these agents must be extensively rinsed prior to use to insure that these noxious chemicals are not transferred to the patient. To maintain the sterility of the bioprosthetic device, this rinsing procedure is performed under sterile conditions in the operating room. Thus, the efficacy of rinsing is limited by the operating room conditions. Moreover, the solutions containing such aldehydes pose an environmental hazard to the operating room personnel who are exposed to these chemicals.
Attempts have been made to develop a bioprosthetic devices that can be stored dry. One attempt involves a dehydration process which involves immersing the device into chemical solutions, such as an ethyl alcohol solution, that remove a substantial amount of water from the bioprosthetic tissue component. Such dehydration processes significantly reduce the overall dimensions of the tissue component. Unfortunately, tissue components subject to this dehydration process cannot be successfully rehydrated and returned to substantially their original dimensions. As a result, bioprosthetic devices comprising tissue components that have undergone such dehydration process are not good candidates for implantation.
Accordingly, it is desirable to have new methods for preparing implantable bioprosthetic devices that are suitable for dry storage. A method that allows for controlled rinsing of the chemically cross-linked tissue components and removal of residual unreacted cross-linking agent in an environment outside of the operating room is desirable. A method that provides tissue components that are capable of being restored to substantially their original dimensions following dry storage is especially desirable.
In accordance with the present invention, a method that allows for dry storage of bioprosthetic devices comprising a tissue component is provided. In one embodiment, the method comprises the steps of providing a device comprising a chemically cross-linked animal tissue component; treating the tissue component with an aqueous solution comprising a biocompatible, water soluble, organic molecule comprising a plurality of carbon atoms and a plurality of hydroxyl groups, hereinafter referred to as a xe2x80x9cdimensional stabilizer,xe2x80x9d for a time sufficient to allow equilibration between the fluids in the interstices of the tissue component and the aqueous solution; and then storing the treated tissue component in a sealable container that is essentially free of liquid. In another embodiment, the tissue component is sterilized using a sterilizing gas or ionizing radiation either prior to or after placement in the storage container. The advantages to dry storage of implantable tissue components include the reduced size, volume and weight of the product as compared to implantable tissue stored in a fluid medium in glass or plastic containers, and elimination of noxious fluids associated with storage of tissue components in aldehyde solutions.
The present invention also relates to an implantable tissue component that can be stored dry. The tissue component and comprises within the interstices thereof a dimensional stabilizer selected from the group consisting of a polyhydric alcohol and derivatives thereof, a water soluble carbohydrate, and a water soluble gum. In another embodiment, the tissue component is chemically-fixed. The tissue component is disposed within the chamber of a package, the chamber being defined by one or more members formed from a material that is resistant to penetration by micro-organisms, particularly bacteria and fungi. Preferably, at least a portion of one or more of the members is gas-permeable. The chamber and tissue component are sterile and essentially free of an aldehyde solution. Except for the liquids contained within the interstices of the tissue component, the chamber is also essentially free of liquid.
The present invention further relates to a method of preparing a bioprosthetic device comprising a tissue component for implantation into a patient. The method comprises obtaining a bioprosthetic device comprising a tissue component that is chemically-fixed and comprises within the interstices thereof a dimensional stabilizer selected from the group consisting of a polyhydric alcohol and derivatives thereof, a water soluble carbohydrate, and a water soluble gum; and rehydrating the tissue component in an aqueous solution.